The goal of this project is to analyze quantitatively infections by primary patient (PR) and laboratory-adapted (LA) isolate viruses and to learn how differences in CD4 affinities affect cellular tropisms. The first of the investigator's three specific aims is to study quantitatively adsorption and penetration of PR and LA T cell-tropic HIV isolates into CD4- positive cells using cell clones with diverse amounts of CD4. The author proposes to study the kinetics of the steps of HIV attachment and to determine the order of CD4 involvement in each step. He will identify cellular factor(s) other than CD4 that limit attachment of LA viruses and their placement in the infection pathway. The second aim is to use molecularly cloned env genes of PR and LA viruses and of mutant viruses that have reduced CD4 affinities, and to identify features of env glycoproteins that control discrete steps of viral entry pathways. The third aim is to learn how absorptive properties of PR viruses change throughout disease progression. The fourth and last aim is to develop a novel system to study gp120- gp41- and CD4-dependent cell-cell fusion and to use it to study and possibly to clone cDNAs for cellular accessory factors.